Ines C Osma-Garcia, Orlane Maloudi, Mailys Mouysset, Dunja Capitan-Sobrino, Trang-My M Nguyen, Yann Aubert, Manuel D. Diaz-Munoz
{"title":"TIA1 和 TIAL1 的转录后调控控制着强化 T 细胞静止的转录程序。","authors":"Ines C Osma-Garcia, Orlane Maloudi, Mailys Mouysset, Dunja Capitan-Sobrino, Trang-My M Nguyen, Yann Aubert, Manuel D. Diaz-Munoz","doi":"10.1101/2024.09.03.608755","DOIUrl":null,"url":null,"abstract":"Immune protection against new and recurrent infections relies on long-term maintenance of a highly diversified T-cell repertoire. Transcription factors cooperate to enforce T-cell metabolic quiescence and maintenance. However, less is known about the post-transcriptional networks that preserve peripheral naive T cells. Here we describe the RNA binding proteins TIA1 and TIAL1 as key promoters of CD4 and CD8 T cell quiescence. T cells deficient in TIA1 and TIAL1 undergo uncontrolled cell proliferation in the absence of cognate antigens, leading this to a premature T-cell activation, exhaustion and death. Mechanistically, TIA1 and TIAL1 control the expression of master regulatory transcription factors, FOXP1, LEF1 and TCF1, that restrain homeostatic T-cell proliferation. In summary, our study highlights a previously unrecognised dependency on post-transcriptional gene regulation by TIA1 and TIAL1 for implementing the quiescent transcriptional programs for long survival of T cells.","PeriodicalId":501182,"journal":{"name":"bioRxiv - Immunology","volume":"58 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Post-transcriptional regulation by TIA1 and TIAL1 controls the transcriptional program enforcing T cell quiescence.\",\"authors\":\"Ines C Osma-Garcia, Orlane Maloudi, Mailys Mouysset, Dunja Capitan-Sobrino, Trang-My M Nguyen, Yann Aubert, Manuel D. Diaz-Munoz\",\"doi\":\"10.1101/2024.09.03.608755\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Immune protection against new and recurrent infections relies on long-term maintenance of a highly diversified T-cell repertoire. Transcription factors cooperate to enforce T-cell metabolic quiescence and maintenance. However, less is known about the post-transcriptional networks that preserve peripheral naive T cells. Here we describe the RNA binding proteins TIA1 and TIAL1 as key promoters of CD4 and CD8 T cell quiescence. T cells deficient in TIA1 and TIAL1 undergo uncontrolled cell proliferation in the absence of cognate antigens, leading this to a premature T-cell activation, exhaustion and death. Mechanistically, TIA1 and TIAL1 control the expression of master regulatory transcription factors, FOXP1, LEF1 and TCF1, that restrain homeostatic T-cell proliferation. In summary, our study highlights a previously unrecognised dependency on post-transcriptional gene regulation by TIA1 and TIAL1 for implementing the quiescent transcriptional programs for long survival of T cells.\",\"PeriodicalId\":501182,\"journal\":{\"name\":\"bioRxiv - Immunology\",\"volume\":\"58 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"bioRxiv - Immunology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/2024.09.03.608755\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv - Immunology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.09.03.608755","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
针对新感染和复发性感染的免疫保护依赖于高度多样化的 T 细胞库的长期保持。转录因子通力合作,强制T细胞代谢静止和维持。然而,人们对维持外周幼稚 T 细胞的转录后网络知之甚少。在这里,我们描述了作为 CD4 和 CD8 T 细胞静止的关键启动子的 RNA 结合蛋白 TIA1 和 TIAL1。缺乏 TIA1 和 TIAL1 的 T 细胞在缺乏同源抗原的情况下会发生不受控制的细胞增殖,导致 T 细胞过早活化、衰竭和死亡。从机理上讲,TIA1 和 TIAL1 可控制主调节转录因子 FOXP1、LEF1 和 TCF1 的表达,从而抑制同源性 T 细胞增殖。总之,我们的研究强调了以前未认识到的 TIA1 和 TIAL1 对转录后基因调控的依赖性,TIA1 和 TIAL1 可实施静息转录程序,使 T 细胞长期存活。
Post-transcriptional regulation by TIA1 and TIAL1 controls the transcriptional program enforcing T cell quiescence.
Immune protection against new and recurrent infections relies on long-term maintenance of a highly diversified T-cell repertoire. Transcription factors cooperate to enforce T-cell metabolic quiescence and maintenance. However, less is known about the post-transcriptional networks that preserve peripheral naive T cells. Here we describe the RNA binding proteins TIA1 and TIAL1 as key promoters of CD4 and CD8 T cell quiescence. T cells deficient in TIA1 and TIAL1 undergo uncontrolled cell proliferation in the absence of cognate antigens, leading this to a premature T-cell activation, exhaustion and death. Mechanistically, TIA1 and TIAL1 control the expression of master regulatory transcription factors, FOXP1, LEF1 and TCF1, that restrain homeostatic T-cell proliferation. In summary, our study highlights a previously unrecognised dependency on post-transcriptional gene regulation by TIA1 and TIAL1 for implementing the quiescent transcriptional programs for long survival of T cells.